S184: EVALUATING TECLISTAMAB IN PATIENTS WITH RELAPSED/ REFRACTORY MULTIPLE MYELOMA FOLLOWING EXPOSURE TO OTHER B-CELL MATURATION ANTIGEN (BCMA)-TARGETED AGENTS
Authors: C. Touzeau, A. Krishnan, P. Moreau, A. Perrot, S. Z. Usmani, S. Manier, M. Cavo, C. Martinez-Chamorro, A. Nooka, T. Martin, L. Karlin, X. Leleu, N. Bahlis, B. Besemer, L. Pei, R. Verona, S. Girgis, C. Uhlar, R. Kobos, A. Garfall
Journal: HemaSphere (2022)

Background: Teclistamab (JNJ-64007957) is a T cell redirecting bispecific antibody that targets both B-cell maturation antigen (BCMA) and CD3 receptors to induce T cell mediated cytotoxicity of BCMA-expressing myeloma cells. MajesTEC-1 is an open-label, multicohort, phase 1/2 study evaluating teclistamab in patients (pts) with relapsed/ refractory multiple myeloma (RRMM) previously treated with ≥3 prior lines of therapy (LOT). An overall response rate (ORR) of 62.0% in pts with no prior anti-BCMA treatment (tx) was previously reported in a pooled analysis from phase 1 and phase 2 cohort A at a median follow-up of 7.8 mo. Aims: We report efficacy and safety results of teclistamab from cohort C, which enrolled patients who had prior exposure to anti-BCMA treatment. Methods: Eligible pts (age ≥18 y) had multiple myeloma (MM) per IMWG criteria and were previously treated with ≥3 prior LOT, including a PI, IMiD, anti-CD38 antibody, and anti-BCMA treatment (chimeric antigen receptor T cell therapy [CAR-T] or Ab drug conjugate [ADC]). Pts were enrolled using a Simon's stage design to receive weekly subcutaneous teclistamab 1.5 mg/kg (step-up doses of 0.06 and 0.3 mg/kg). ORR per IMWG 2016 criteria was the primary endpoint. All AEs were graded per CTCAE v4.03; immune effector cell–associated neurotoxicity syndrome (ICANS) and cytokine release syndrome (CRS) were graded per ASTCT guidelines. Results: In cohort C, 38 pts (median age 63.5 y [range 32–82]; 63% male) received teclistamab (median prior LOT 6 [range 3–14]) at the data cutoff date of Sep 7, 2021. Of the 38 patients, 25 (66%) were refractory to an anti-BCMA treatment, and 32 (84%) were refractory to last LOT. Among 25 efficacy-evaluable patients, 16 (64%) received prior ADC, 11 (44%) received prior CAR-T, and 2 pts received both. The ORR was 40% (95% CI, 21–61) at a median follow-up of 6.9 mo (range 0.7–8.7). Complete response or better were observed in 5 pts (20%). In ADC-exposed and CAR-T-exposed pts, the ORR was 38% (95% CI, 15–65) and 45% (95% CI, 17–77), respectively. Responses were rapid in most, with deepening of responses over time in 7 of 25 pts. While the median duration of response was not reached, median time to first response was 1.2 mo (range, 0.2–4.9) and to best response was 2.1 mo (range, 1.1–5.7). No new safety concerns were observed, and the safety profile was comparable with that of BMCA tx-naive pts. Infections were reported in 16 pts (42%; grade 3/4, 26%). Most common AEs (n=38) were CRS (63%; all grade 1/2; median time to CRS onset: 3 d [range, 2–6], duration of CRS: 2 d [range, 1–4]), thrombocytopenia (42%; grade 3/4, 29%), neutropenia (55%; grade 3/4, 50%), lymphopenia (40%; grade 3/4, 37%), and anemia (39%; grade 3/4 29%), Grade 3 ICANS was reported in 1 pt which resolved with supportive care and the pt remained on tx. Anti-teclistamab Abs were not detected in any pts. Baseline BCMA expression levels were comparable with those reported in BCMA tx-naive pts. Updated efficacy and safety results will be presented for 40 pts. Summary/Conclusion: These preliminary results observed with serial targeting of BCMA with teclistamab following ADC or CAR-T tx suggest a promising ORR with early responses that deepen over time. Additionally, a well-tolerated safety profile was observed in patients treated with anti-BCMA tx.